Chronic obstructive pulmonary

disease (COPD)
Sultan Chaudhry, Benny Dua and Eric Wong

 Faculty reviewer: Dr. Marianne Talman, Associate Professor, Department of Medicine,

McMaster University

Definition
Lancet. 2012 Apr 7;379(9823):1341-51.
Am J Respir Crit Care Med. 2007 Sep 15;176(6):532-55.

COPD is a characterized by persistent airflow limitation that is usually

progressive and associated with an enhanced chronic inflammatory response
in the airways and lung to noxious particles or gases.

Asthma vs COPD

Asthma = fully reversible airway narrowing

COPD = not fully reversible airway narrowing

COPD can be divided into 2 clinical phenotypes: emphysema and chronic

bronchitis.

 Emphysema is defined pathologically as enlargement of distal air spaces.

 Chronic bronchitis is defined clinically as cough productive of sputum occurring on
most days in 3 consecutive months over 2 consecutive years.

Etiology
 Lancet. 2012 Apr 7;379(9823):1341-51.
 Am J Respir Crit Care Med. 2007 Sep 15;176(6):532-55.
 Lancet. 2009 Aug 29;374(9691):733-43.

Many factors contribute to the development of COPD, including genetic

factors like alpha1-antitrypsin deficiency, occupational exposures to dusts
and chemicals, pollution, respiratory infections in childhood and cigarette
smoke.

Etiology Mechanism(s)

Cigarette smoke Presence of smoke particles in the lungs leads to an

inflammatory response with increased macrophage and
 neutrophil infiltration into the lungs. These immune cells
release cytokines, chemokines and elastases, which
damages the lung parenchyma over time.

Occupational Etiology unclear, however, is hypothesized to be a similar

exposures to inflammatory response that damages the alveoli.
dust and
chemicals

Alpha-1 Alpha-1 antitrypsin is a serine protease inhibitor (SERPIN)

antitrypsin secreted by the liver into the blood which inhibits the
deficiency enzyme neutrophil elastase from damaging the lung
tissue. Deficiency of this alpha-1 antitrypsin leads
to unopposed elasteolysis (destruction of the elastin
fibers in alveolar walls) and development of early
emphysema. This is the protease-antiprotease
hypothesis of emphysema development.

Chronic IV drug IV drug users of cocaine, methadone and heroin are at

use higher risk for developing COPD; this is attributed to
the vascular damage induced by the insoluble
filler (cornstarch, cellulose, talc, fiber etc) found in IV
drugs.

Pathogenesis, pathophysiology and clinical

features
BMJ. 2006 May 20; 332(7551): 1202–1204.

Though a breakdown of COPD into emphysema and chronic bronchitis is

helpful, typically patients have features and findings of each and cannot
be simply classified.

Emphysema Chronic bronchitis

Pathogenesis The inflammatory Mucous gland enlargement,

response, mediated by goblet cell hyperplasia and
Am J Respir Cell neutrophils, macrophages mucociliary dysfunction occur
Mol Biol. 2005 and CD8+ T-cells, release in larger airways, causing
May;32(5):367-7 inflammatory mediators excessive mucus production
2. and enzymes that and build-up reducing the
damage the lung airway lumen.Although these
parenchyma. Proteases pathological changes in the
 like elastase and matrix large airways, it appears that
metalloproteinases the major site of increased
(MMPs) released by airway resistance is the
these inflammatory cells small airways (≤
break down the 2mm). Fibrosis and smooth
connective tissue of the muscle hypertrophy may
alveolar walls and the occur along with excess
septae. A loss of elastic mucus
recoil leads production and cellular
to diminished expiratory infiltration in the peripheral
flow rates, air trapping airways.
and airway collapsing.

Pathophysiolog Parenchymal Small airway

y destruction: Recurrent inflammation: Mechanisms
damage to the alveoli discussed above lead to
BMJ. 2006 May eventually leads to septal inflammation in the smaller
20; 332(7551): destruction along with the bronchioles and mucus
1202–1204. capillary bed also. secretions further narrow the
airway lumen. Despite this, the
Matched V/Q defect: parenchyma are relatively less
Since both the terminal damaged.
bronchioles and alveoli
along with the capillary V/Q mismatch: The
bed have been destroyed, physiologic response leads to a
a matched defect exists drop in ventilation and
between the ventilation compensation with the rise in
and perfusion; areas of CO. Increased perfusion in the
low ventilation also have areas of poor ventilation takes
poor perfusion. place eventually causing
hypoxia and secondary
Mild hypoxia: Despite polycythemia.
the “matched” V/Q defect,
overtime hyperventilation Severe hypoxia and
develops and cardiac hypercarbia: Chronic V/Q
output (CO) drops which mismatch leads to decreased
leads to areas of poor oxygenation/deoxygenation of
blood flow in relatively the blood resulting in
well oxygenated areas. hypoxemia and increased CO2
Due to this poor CO, the retention (respiratory acidosis
rest of the body suffers ensues).
from tissue hypoxia.
Pulmonary hypertension and
Cachexia: At the cor pulmonale: Chronic
pulmonary level, the low hypercapnia and respiratory
CO leads to pulmonary acidosis lead to arterial
 cachexia; which induces vasoconstriction in the lungs.
weight loss and muscle With the retrograde pressure
wasting. This gives these build-up, the right ventricular
patients the characteristic pressures continue to rise and
“pink-puffer” eventually causing RV failure.
appearance. Otherwise, known as cor
pulmonale.
Clinical “Pink puffer” – type A “Blue bloater” – type B
signs/symptom
s Severe constant Copious sputum production:
dyspnea/tachypnia High amount of sputum
(“puffing”): Likely related produced by the goblet
to increasing cells. See Pathogenesis
end-expiratory volume above.
(decreased recoil),
making each breath less Cough: Irritation of the cough
efficient. Patients use receptors, by the mucous, in
accessory muscles (tripod the smaller and the large
position) and breath faster airways.
(hyperventilation) to
compensate for feeling of Cyanotic (“blue”): The
inadequate ventilation. mismatched V/Q defect leads
Dyspnea is also related to to inadequate oxygenation of
respiratory muscle fatigue the blood; most prominent in
from increased use as the lips and the nail beds.
well as the flattening of
the diaphragm which Volume overload
impairs its function. (“bloater”): Most likely from
Am J Respir Crit Care from the right ventricular (RV)
Med. 2008 Mar failure, known as cor
15;177(6):564-5. pulmonale.

Mild cough: Irritation of Wheezy on auscultation: Due

the smaller airway can to airway obstruction.
lead to the production of Compared to asthma, there is
cough. less bronchospasm and more
mucus/hypertrophy in COPD.
Non cyanotic
(“pink”): Matched V:Q Rhonchi is a gurgling sound
defect; no hypoxemia. that may be heard due to
mucus hypersecretion in the
Thin/cachexic: Loss of airways.
skeletal muscle and
subcutaneous fat due to
inadequate oral intake as
 well as high levels of
inflammatory cytokines
(TNF-α) that cause such
wasting.

Diminished breath
sounds on
auscultation: Hyperinflati
on of alveoli and
destruction of alveolar
architecture causes
decreased airway
resistance.

Exacerbations
N Engl J Med. 2012 Jul 26;367(4):340-7.

Several studies have shown some link between bacterial colonization of the
upper and the lower airways of patients and acute exacerbations of COPD.
Furthermore, exacerbations seem to coincide with the rise in acute respiratory
viral infections (influenza, parovirus etc). The pathogens introduce new
antigens into the airways and the parenchyma which induces the secretion of
chemokines (TNF-α and IL-6, IL-8 etc) and leukotrienes, both by the airway
macrophages as well as the epithelium, which recruit neutrophils. These
neutrophils, along with other immune cells secrete proteases and other
media that further inflame the airways and destroy bronchial epithelium,
leading to a clinical exacerbation.

Treatment
 Am J Respir Crit Care Med. 2013 Feb 15;187(4):347-65.
 Lancet. 2012 Apr 7;379(9823):1341-51.
 N Engl J Med. 2012 Jul 26;367(4):340-7.

Smoking cessation

Smoking cessation significantly slows progression of lung function decline

and reduces mortality by 18%. It is the single most effective and important
intervention in COPD.

Bronchodilators
Inhaled β2-agonists (e.g. short-acting salbutamol or long-acting salmeterol)
act on β2-receptors on smooth muscle cells to cause bronchodilation. Inhaled
anticholinergics (e.g. short-acting ipratropium or long-acting tiotropium) act to
block acetylcholine’s effect on muscarinic receptors on smooth muscle cells,
allowing bronchodilation. Inhaled β2-agonists and anticholinergics are used for
both symptomatic management, as well as acute exacerbations of COPD.
Long-acting bronchodilators are preferred over short-acting ones because of
fewer doses and improved symptom management. For more effective treat of
stable COPD, combination therapy using an inhaled β 2-agonist and an
anticholinergic can also be used.

Corticosteroids

Steroids suppress the inflammatory response by inhibiting transcriptions

factors, including nuclear factor-κB, that regulate the transcription of various
cytokines, chemokines, adhesion molecules, and other proteins that induce
and perpetuate inflammation. Inhaled corticosteroids are not used for the
treatment of COPD exacerbations; however, have been used in the long-term
treatment of COPD in a minority of patients with stable COPD who
demonstrate frequent exacerbations and bronchodilator reversibility. Systemic
corticosteroids are recommended to be used during an acute exacerbation
requiring hospitalization.

Bronchodilators and corticosteroids have not been shown to reduce

mortality; they only improve FEV1, symptoms, and quality of life.

Oxygen

Cochrane Database Syst Rev. 2005 Oct 19;(4):CD001744.

Oxygen therapy is frequently provided along with pharmacological

interventions to treat underlying hypoxemia in COPD patients. By reducing
hypoxia in the alveoli, pulmonary vasoconstriction is reduced. Reducing
pulmonary hypertension lowers right heart afterload, and improves right heart
systolic function. Oxygen also reduces hypoxemia in the blood, which reduces
the risk of developing polycythemia. However, oxygen therapy has only been
shown to reduce mortality in those with severe hypoxemia (PaO2 < 55mmHg);
otherwise there is no mortality benefit.

Pulmonary rehabilitation

Chest. 2007 May;131(5 Suppl):4S-42S.

The goal of pulmonary rehabilitation is to improve quality of life and daily

functioning in COPD patients. Through a multidisciplinary team, patients are
typically enrolled in a 6-12 week program that includes exercise training,
psychosocial support, nutritional improvement, and education. Numerous
studies (see Chest reference) have shown improvement in exercise capacity,
better quality of life, and decreased hospitalizations. However, mortality is
unchanged.

Lung volume reduction surgery (LVRS)

Ann Thorac Surg. 2006 Aug;82(2):431-43.